tbuckley/cabot-search huggingface dataset:
Prevalence of skin sensitization and dermatitis among epoxy-exposed workers in the wind turbine industry
Authors: Alexandra G. Christiansen, Ole Carstensen, Mette Sommerlund, Per A. Clausen, Jakob H. Bønløkke, Vivi Schlünssen, Marléne Isaksson, Sigrun A. J. Schmidt, Henrik A. Kolstad
Journal: British Journal of Dermatology (2022)

A high prevalence of skin sensitization and dermatitis has been reported among workers exposed to epoxy components.To estimate the risk of skin sensitization and dermatitis among workers exposed to epoxy components during production of wind turbine blades while using comprehensive safety measures.A cross-sectional study of 180 highly epoxy-exposed production workers and 41 nonexposed office workers was conducted at two wind turbine blade factories in Denmark. Participants underwent a skin examination, were tested with a tailored patch test panel including epoxy-containing products used at the factories, and answered a questionnaire.Sixteen production workers (8·9%) were sensitized to an epoxy component compared with none of the office workers. Skin sensitization was more frequent within the first year of exposed employment. Strong selection bias by atopic status was indicated. Among nonatopic workers, the prevalence of dermatitis was higher among production workers (16·4%) than among office workers [6·5%, odds ratio (OR) 2·3, 95% confidence interval (CI) 0·6-9·1] and higher among the sensitized workers (43·8%) than the nonsensitized workers (14·6%, OR 4·5, 95% CI 1·6-12·7). Resins based on diglycidyl ether of bisphenol A and F were the most frequent sensitizers. One of the four workers sensitized to epoxy components used at the factories did not react to the epoxy resin of the TRUE test® panel.Despite comprehensive skin protection, sensitization and dermatitis are prevalent among highly epoxy-exposed workers in the wind turbine industry in Denmark. Our findings document the need for intensified preventive efforts and emphasize the importance of tailored patch testing. What is already known about this topic? Epoxy components are well-known sensitizers of the skin. A high prevalence of skin sensitization and dermatitis has been reported among workers exposed to epoxy components. Comprehensive protective equipment is recommended when working with epoxy components. What does this study add? Despite comprehensive skin protection, skin sensitization and dermatitis are prevalent among epoxy-exposed workers. We found that 40% of workers sensitized to epoxy products had dermatitis. Only 75% of the sensitized workers were detected by the epoxy resin of the TRUE test® , which emphasizes the importance of tailored testing.
Impact of Macintosh blade size on endotracheal intubation success in intensive care units: a retrospective multicenter observational MacSize-ICU study
Authors: Thomas Godet, Audrey De Jong, Côme Garin, Renaud Guérin, Benjamin Rieu, Lucile Borao, Bruno Pereira, Nicolas Molinari, Jean-Etienne Bazin, Matthieu Jabaudon, Gérald Chanques, Emmanuel Futier, Samir Jaber
Journal: Intensive Care Medicine (2022)

To investigate the impact of Macintosh blade size used during direct laryngoscopy (DL) on first-attempt intubation success of orotracheal intubation in French intensive care units (ICUs). We hypothesized that success rate would be higher with Macintosh blade size No3 than with No4. Multicenter retrospective observational study based on data from prospective trials conducted in 48 French ICUs of university, and general and private hospitals. After each intubation using Macintosh DL, patients' and operators' characteristics, Macintosh blade size, results of first DL and alternative techniques used, as well as the need of a second operator were collected. Complications rates associated with intubation were investigated. Primary outcome was success rate of first DL using Macintosh blade. A total of 2139 intubations were collected, 629 with a Macintosh blade No3 and 1510 with a No4. Incidence of first-pass intubation after first DL was significantly higher with Macintosh blade No3 (79.5 vs 73.3%, p = 0.0025), despite equivalent Cormack–Lehane scores (p = 0.48). Complications rates were equivalent between groups. Multivariate analysis concluded to a significant impact of Macintosh blade size on first DL success in favor of blade No3 (OR 1.44 [95% CI 1.14–1.84]; p = 0.0025) without any significant center effect on the primary outcome (p = 0.18). Propensity scores and adjustment analyses concluded to equivalent results. In the present study, Macintosh blade No3 was associated with improved first-passed DL in French ICUs. However, study design requires the conduct of a nationwide prospective multicenter randomized trial in different settings to confirm these results.
Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission
Authors: Gabriele Gamerith, Finn Mildner, Peter A Merkel, Kristina Harris, Laura Cooney, Noha Lim, Robert Spiera, Philip Seo, Carol A Langford, Gary S Hoffman, E William St Clair, Fernando C Fervenza, Paul Monach, Steven R Ytterberg, Duvuru Geetha, Arno Amann, Dominik Wolf, Ulrich Specks, John H Stone, Andreas Kronbichler
Journal: Annals of the Rheumatic Diseases (2022)

Objectives We investigated whether soluble immune checkpoints (sICPs) predict treatment resistance, relapse and infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Methods Plasma sICP concentrations from available samples obtained during conduct of the RAVE trial were measured by immunoabsorbent assays from patients with either proteinase 3 (PR3) or myeloperoxidase (MPO)-ANCA vasculitis and were correlated with clinical outcomes, a set of biomarkers and available flow cytometry analyses focusing on T cell subsets. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J. Results Analysis of 189 plasma samples at baseline revealed higher concentrations of sTim-3, sCD27, sLag-3, sPD-1 and sPD-L2 in patients with MPO-ANCA vasculitis (n=62) as compared with PR3-ANCA vasculitis (n=127). Among patients receiving rituximab induction therapy (n=95), the combination of lower soluble (s)Lag-3 (&lt;90 pg/mL) and higher sCD27 (&gt;3000 pg/mL) predicted therapy failure. Twenty-four out of 73 patients (32.9%) in the rituximab arm reaching remission at 6 months relapsed during follow-up. In this subgroup, high baseline values of sTim-3 (&gt;1200 pg/mL), sCD27 (&gt;1250 pg/mL) and sBTLA (&gt;1000 pg/mL) were associated with both sustained remission and infectious complications. These findings could not be replicated in 94 patients randomised to receive cyclophosphamide/azathioprine. Conclusions Patients with AAV treated with rituximab achieved remission less frequently when concentrations of sLag-3 were low and concentrations of sCD27 were high. Higher concentrations of sTim-3, sCD27 and sBTLA at baseline predicted relapse in patients treated with rituximab. These results require confirmation but may contribute to a personalised treatment approach of AAV.
Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial
Authors: Saurabh Kedia, Shubi Virmani, Sudheer K Vuyyuru, Peeyush Kumar, Bhaskar Kante, Pabitra Sahu, Kanav Kaushal, Mariyam Farooqui, Mukesh Singh, Mahak Verma, Aditya Bajaj, Manasvini Markandey, Karan Sachdeva, Prasenjit Das, Govind K Makharia, Vineet Ahuja
Journal: Gut (2022)

Objective Microbiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC. Design This open-labelled randomised controlled trial (RCT) randomised patients with mild-moderate (Simple Clinical Colitis Activity Index (SCCAI) 3–9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)&gt;1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) versus optimised standard medical therapy (SMT). The FMT-AID arm received seven weekly colonoscopic infusions of freshly prepared FMT from multiple rural donors(weeks 0–6) with anti-inflammatory diet. Baseline medications were optimised in the SMT arm. Clinical responders (decline in SCCAI &gt; 3) at 8 weeks in both arms were followed until 48 weeks on baseline medications (with anti-inflammatory diet in the FMT-AID arm). Primary outcome measures were clinical response and deep remission (clinical—SCCAI &lt;2; and endoscopic—UCEIS &lt;1) at 8 weeks, and deep remission and steroid-free clinical remission at 48 weeks. Results Of the 113 patients screened, 73 were randomised, and 66 were included in (35—FMT-AID; 31—SMT) modified intention-to-treat analysis (age—35.7±11.1 years; male—60.1%; disease duration—48 (IQR 24–84) months; pancolitis—34.8%; SCCAI—6 (IQR 5–7); UCEIS—4 (IQR 3–5)). Baseline characteristics were comparable. FMT-AID was superior to SMT in inducing clinical response (23/35 (65.7%) vs 11/31 (35.5%), p=0.01, OR 3.5 (95% CI 1.3 to 9.6)), remission (21/35 (60%) vs 10/31 (32.3%), p=0.02, OR 3.2 (95% CI 1.1 to 8.7)) and deep remission (12/33 (36.4%) vs 2/23 (8.7%), p=0.03, OR 6.0 (95% CI 1.2 to 30.2)) at 8 weeks. Anti-inflammatory diet was superior to SMT in maintaining deep remission until 48 weeks (6/24 (25%) vs 0/27, p=0.007). Conclusion Multidonor FMT with anti-inflammatory diet effectively induced deep remission in mild-moderate UC which was sustained with anti-inflammatory diet over 1 year. Trial registration number ISRCTN15475780 .
Meaningful thresholds for patient-reported outcomes following interventions for anterior cruciate ligament tear or traumatic meniscus injury: a systematic review for the OPTIKNEE consensus
Authors: Erin M Macri, James J Young, Lina Holm Ingelsrud, Karim M Khan, Berend Terluin, Carsten Bogh Juhl, Jackie L Whittaker, Adam G Culvenor, Kay M Crossley, Ewa M Roos
Journal: British Journal of Sports Medicine (2022)

Objective We synthesised and assessed credibility (ie, trustworthiness) of thresholds that define meaningful scores for patient-reported outcome measures (PROMs) following interventions for anterior cruciate ligament (ACL) tear or traumatic meniscus injury. Design Systematic review, narrative synthesis. Data sources We searched five databases, handsearched references of included studies and tracked citations. Eligibility Included studies investigated: individuals with ACL tear or meniscus injury; mean age &lt;35 years; and PROM thresholds calculated using any method to define a minimal important change (MIC) or a meaningful post-treatment score (Patient Acceptable Symptom State (PASS) or Treatment Failure). Results We included 18 studies (15 ACL, 3 meniscus). Three different methods were used to calculate anchor-based MICs across 9 PROMs, PASS thresholds across 4 PROMs and treatment failure for 1 PROM. Credibility was rated ‘high’ for only one study—an MIC of 18 for the Knee injury and Osteoarthritis Outcome Score Quality-of-life (KOOS-QOL) subscale (using the MID Credibility Assessment Tool). Where multiple thresholds were calculated among ‘low’ credibility thresholds in ACL studies, MICs converged to within a 10-point range for KOOS-Symptoms (−1.2 to 5.4) and function in daily living (activities of daily living, ADL 0.5–8.1) subscales, and the International Knee Documentation Committee Subjective Knee Form (7.1–16.2). Other PROM thresholds differed up to 30 points. PASS thresholds converged to within a 10-point range in KOOS-ADL for ACL tears (92.3–100), and KOOS-Symptoms (73-78) and KOOS-QOL (53-57) in meniscus injuries. Conclusion Meaningful PROM thresholds were highly susceptible to study heterogeneity. While PROM thresholds can aid interpretability in research and clinical practice, they should be cautiously interpreted.
Continued treatment with nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from SENSCIS-ON
Authors: Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Martina Gahlemann, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland
Journal: Annals of the Rheumatic Diseases (2022)

Objectives In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) versus placebo, with adverse events that were manageable for most patients. An open-label extension trial, SENSCIS-ON, is assessing safety and FVC decline during longer term nintedanib treatment. Methods Patients who completed the SENSCIS trial or a drug–drug interaction (DDI) study of nintedanib and oral contraceptive on treatment were eligible to enter SENSCIS-ON. Adverse events and changes in FVC over 52 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON (‘continued nintedanib’ group) and in patients who received placebo in SENSCIS and initiated nintedanib in SENSCIS-ON or who received nintedanib for ≤28 days in the DDI study (’initiated nintedanib’ group). Results There were 197 patients in the continued nintedanib group and 247 in the initiated nintedanib group. Diarrhoea was reported in 68.0% and 68.8% of patients in these groups, respectively. Adverse events led to discontinuation of nintedanib in 4.6% and 21.5% of the continued nintedanib and initiated nintedanib groups, respectively. Mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were −58.3 (15.5) mL in the continued nintedanib group and −44.0 (16.2) mL in the initiated nintedanib group. Conclusions The safety profile of nintedanib over 52 weeks of SENSCIS-ON was consistent with that reported in SENSCIS. The change in FVC over 52 weeks of SENSCIS-ON was similar to that observed in the nintedanib group of SENSCIS.
Low-dose interleukin-2 therapy in active systemic lupus erythematosus (LUPIL-2): a multicentre, double-blind, randomised and placebo-controlled phase II trial
Authors: Jens Y Humrich, Patrice Cacoub, Michelle Rosenzwajg, Fabien Pitoiset, Hang Phuong PHAM, Joel Guidoux, David Leroux, Thomas Vazquez, Gabriela Riemekasten, Josef S Smolen, George Tsokos, David Klatzmann
Journal: Annals of the Rheumatic Diseases (2022)

Objectives A regulatory T cell (Treg) insufficiency due to shortage of interleukin-2 (IL-2) is central to the pathophysiology of systemic lupus erythematosus (SLE). We performed a multicentre, double-blinded, randomised, placebo-controlled phase II proof-of-concept trial to evaluate the efficacy of low-dose IL-2 therapy in patients with SLE having moderate-to-severe disease activity while receiving standard treatment. Methods We randomly assigned 100 patients in a 1:1 ratio to receive either 1.5 million IU/day of subcutaneous IL-2 (ILT-101) or placebo for 5 days followed by weekly injections for 12 weeks. Clinical efficacy was assessed at week 12 in a predefined hierarchical analysis of (1) the SLE responder index-4 (SRI-4) response as a primary end point, and of (2) relative and (3) absolute changes in the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index scores as key secondary end points. Results The primary end point was not met in the intention-to-treat population (ILT-101: 68%, placebo: 58%; p=0.3439), due to a 100% SRI-4 response rate in the placebo group from the two sites from Bulgaria. A post hoc per-protocol analysis on a prespecified population that excluded patients from these two sites (n=53) showed a statistically significant difference for the SRI-4 response rate (ILT-101: 83.3%; placebo: 51.7%; p=0.0168), and for the two key secondary end points, accompanied by differences in several secondary exploratory end points. ILT-101 was well tolerated and there was no generation of antidrug antibodies. Conclusions The post hoc hierarchical analysis of the primary and key secondary end points in a per-protocol population, complemented by the exploratory analyses of multiple other secondary end points, support that low-dose IL-2 is beneficial in active SLE. Trial registration number NCT02955615 .
Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α
Authors: Alexis Mathian, Paul Breillat, Karim Dorgham, Paul Bastard, Caroline Charre, Raphael Lhote, Paul Quentric, Quentin Moyon, Alice-Andrée Mariaggi, Suzanne Mouries-Martin, Clara Mellot, François Anna, Julien Haroche, Fleur Cohen-Aubart, Delphine Sterlin, Noël Zahr, Adrian Gervais, Tom Le Voyer, Lucy Bizien, Quentin Amiot, Micheline Pha, Miguel Hié, Francois Chasset, Hans Yssel, Makoto Miyara, Pierre Charneau, Pascale Ghillani-Dalbin, Jean-Laurent Casanova, Flore Rozenberg, Zahir Amoura, Guy Gorochov
Journal: Annals of the Rheumatic Diseases (2022)

Objectives Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown. Methods We retrospectively analysed a monocentric longitudinal cohort of 609 patients with SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed by abolishment of Madin-Darby bovine kidney cell protection by IFN-α2 against vesicular stomatitis virus challenge. Serum-neutralising activity against IFN-α2, IFN-β and IFN-ω was also determined with a reporter luciferase activity assay. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns. Results Neutralising and non-neutralising anti-IFN-α antibodies are present at a frequency of 3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-α, unlike non-neutralising AAbs, are associated with reduced IFN-α serum levels and a reduced likelihood to develop active disease. However, they predispose patients to an increased risk of herpes zoster and severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE is mostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-α AAbs do not interfere with COVID-19 vaccine humoral immunogenicity. Conclusion The production of non-neutralising and neutralising anti-IFN-I antibodies in SLE is likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficial effect on disease activity, yet a greater viral risk. This finding reinforces the recommendations for vaccination against SARS-CoV-2 in SLE.
Universal healthcare coverage and health service delivery before and during the COVID-19 pandemic: A difference-in-difference study of childhood immunization coverage from 195 countries
Authors: Sooyoung Kim, Tyler Y. Headley, Yesim Tozan
Journal: PLoS Medicine (2022)

Several studies have indicated that universal health coverage (UHC) improves health service utilization and outcomes in countries. These studies, however, have primarily assessed UHC's peacetime impact, limiting our understanding of UHC's potential protective effects during public health crises such as the Coronavirus Disease 2019 (COVID-19) pandemic. We empirically explored whether countries' progress toward UHC is associated with differential COVID-19 impacts on childhood immunization coverage.
The Medical Student's Manual of Chemistry.
Journal: JAMA (1907)

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Blocking CCL8-CCR8–Mediated Early Allograft Inflammation Improves Kidney Transplant Function
Authors: Anil Dangi, Irma Husain, Collin Z. Jordan, Shuangjin Yu, Naveen Natesh, Xiling Shen, Jean Kwun, Xunrong Luo
Journal: Journal of the American Society of Nephrology (2022)

In kidney transplantation, early allograft inflammation impairs long-term allograft function. However, precise mediators of early kidney allograft inflammation are unclear, making it challenging to design therapeutic interventions.We used an allogeneic murine kidney transplant model in which CD45.2 BALB/c kidneys were transplanted to CD45.1 C57BL/6 recipients.Donor kidney resident macrophages within the allograft expanded rapidly in the first 3 days. During this period, they were also induced to express a high level of Ccl8, which, in turn, promoted recipient monocyte graft infiltration, their differentiation to resident macrophages, and subsequent expression of Ccl8. Enhanced graft infiltration of recipient CCR8+ T cells followed, including CD4, CD8, and γδ T cells. Consequently, blocking CCL8-CCR8 or depleting donor kidney resident macrophages significantly inhibits early allograft immune cell infiltration and promotes superior short-term allograft function.Targeting the CCL8-CCR8 axis is a promising measure to reduce early kidney allograft inflammation.
Image Phenotyping of Preterm-Born Children Using Hyperpolarized<sup>129</sup>Xe Lung Magnetic Resonance Imaging and Multiple-Breath Washout
Authors: Ho-Fung Chan, Laurie J. Smith, Alberto M. Biancardi, Jody Bray, Helen Marshall, Paul J. C. Hughes, Guilhem J. Collier, Madhwesha Rao, Graham Norquay, Andrew J. Swift, Kylie Hart, Michael Cousins, W. John Watkins, Jim M. Wild, Sailesh Kotecha
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood.